A multicompartmental model for cell cycle kinetics was integrated with reaction kinetics of biomarker synthesis, by which based on the concentration measured of a biomarker and the characteristics of its kinetic parameters, one can estimate the total number of tumor cells as well as any variation in number after therapy. This approach was utilized to analyze the effect of 5-azacytidine on the L1210 leukemia- polyamine system. The time-course behavior of cell kinetic parameters, namely the cell cycle time, the growth fraction, and the rate of cell loss examined during tumor growth using the multicompartmental model was in good agreement with experimental data on Ehrlich ascites tumors, L1210 leukemia, JB-1 ascites tumor and Sarcoma 180. The relationship of drug- tumor interactions was also investigated by taking into consideration three modes of drug action: (a) cell kill, (b) progression delay, or accumulation of cells, and (c) elongation of cell cycle times; the effects of BCNU, ara-C, and MTX on the proliferation kinetics of L1210 leukemia are investigated by computer simulation and favorably compared with available experimental data. Cell kinetic responses of chemotherapy were presented in terms of perturbation of the cell age, cell size, and DNA content distributions and were evaluated with reference to the effect of cell cycle stage- specific agents such as ara-C on spontaneous AKR leukemia. Further attempt was made to design optimal antitumor drug schedules by integrating the discrete-time kinetic model for chemotherapy with an optimization scheme in engineering studies.